The principal aim of these investigations is the study of the molecular structure and genetic regulation of exogenous and endogenous type C mammalian retroviruses. Using techniques of molecular cloning, nucleic acid hybridization and nucleotide sequencing, endogenous MuLV-related proviral DNAs from normal mouse, monkey, and human cells have been extensively characterized. In the mouse system results have been obtained that indicate that 1) the majority of endogenous MuLV envelope (env) sequences are related to neither ecotropic nor xenotropic analogues but appear to be precursors of gene segments encoding MCF MuLV env determinants; and 2) the LTR component of endogenous MuLV proviruses differs from the LTRs of known infectious viruses by containing a unique, highly conserved 105 bp insertion located in the U3 region between the 72 bp direct repeat and the CAAT box. Twenty-nine different MuLV-related segments have been molecularly cloned from human DNA. Nucleotide sequencing studies have shown that the regions coding for pol, and the p30 and p10 gag polypeptides are highly conserved and collinear with those specifying the same gene products in Moloney MuLV.